The studies proposed in this project continue to follow the major aspects of the original research plan. Although alcohol, barbiturates, varios narcotics (e.g., morphine, heroin, and methadone), enkephalins and certain hallucinogens (e.g., phencyclidine, LSD, mescaline) are known to affect the cardiovascular system, very little definitive work has been done in relation to their effects on peripheral and cerebral blood vessels. The studies proposed in this project will continue to focus on in-vivo (microcirculation) and isolated mammalian blood vessels and will: 1. Determine whether acute administration of ethanol, barbiturates, narcotics, narcotic antagonists, primary metabolites of ethanol (i.e., acetaldehyde, acetate), enkephalins and certain hallucinogens have direct musculotropic actions on vascular smooth muscle. 2. Determine the site(s) of action of these drugs in the microcirculation (e.g., arterioles, metarterioles, venules or precapillary sphincters). 3. Determine whether these drugs affect blood vessels by virtue of indirect actions. 4. Determine whether tolerance and/or addition to these narcotic drugs, barbiturates and alcohol change the characteristics of vascular smooth muscle. 5. Search for antagonists to the vasodepressant actions of these drug molecules. 6. Explore role of endothelial cells in the relaxant actions of these molecules. 7. Having documented the foregoing as a frame of reference, ionic and biochemical mechanisms of possible drug action will be explored. 8. Explore sex hormones and aging in relation to the peripheral circulatory actions of alcohol, barbiturates and narcotics. 9. Determine whether these drug molecules exert similar actions on primate airway and vascular muscles.